Lipid metabolism in mycobacteria—Insights using mass spectrometry-based lipidomics

Crick, Peter J.; Guan, Xue Li

doi:10.1016/j.bbalip.2015.10.007

Cited by 15 publications

(12 citation statements)

References 49 publications

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“…One of the bottlenecks of systems scale analyses of metabolites and lipids are the chemical diversity of these biomolecules, which limits the coverage of the metabolome and lipidome. The applications of lipidomics and metabolomics in mycobacterial research is increasingly common [6,145,146] and in fact databases for Mtb lipids were previously established to facilitate identification of mycobacterial lipids [79,147]. To expand on the coverage of metabolomes, a multiplatform approach can be undertaken, for instance by using nuclear magnetic resonance and mass spectrometry, or to employ distinct separation techniques, including chromatography or ion mobility, to capture metabolite subsets, which vary in their specific physiochemical properties.…”

Section: Systems Biology Methodology and Novel Applications In Mtb Researchmentioning

confidence: 99%

Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy

Chang

Guan

2021

Metabolites

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a highly successful intracellular pathogen with the ability to withstand harsh conditions and reside long-term within its host. In the dormant and persistent states, the bacterium tunes its metabolism and is able to resist the actions of antibiotics. One of the main strategies Mtb adopts is through its metabolic versatility—it is able to cometabolize a variety of essential nutrients and direct these nutrients simultaneously to multiple metabolic pathways to facilitate the infection of the host. Mtb further undergo extensive remodeling of its metabolic pathways in response to stress and dormancy. In recent years, advancement in systems biology and its applications have contributed substantially to a more coherent view on the intricate metabolic networks of Mtb. With a more refined appreciation of the roles of metabolism in mycobacterial infection and drug resistance, and the success of drugs targeting metabolism, there is growing interest in further development of anti-TB therapies that target metabolism, including lipid metabolism and oxidative phosphorylation. Here, we will review current knowledge revolving around the versatility of Mtb in remodeling its metabolism during infection and dormancy, with a focus on central carbon metabolism and lipid metabolism.

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Section: Systems Biology Methodology and Novel Applications In Mtb Researchmentioning

confidence: 99%

Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy

Chang

Guan

2021

Metabolites

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“…These major biological ramifications make cyclopropane modifications important targets for structural characterization. Existing methods for structural characterization of cyclopropyl lipids include chemical derivatization of CFAs followed by gas-chromatography (GC) mass spectrometry and multistage linear ion trap MS analysis of metal-adducted lipid species. − However, the derivatization methods required for GC analysis of cyclopropyl lipid analysis are time-consuming and are unable to enhance sufficiently the volatilities of all classes of lipids. ,, Multistage MS methods with collisional activation result in fragmentation at multiple locations adjacent to the cyclopropane ring, yielding convoluted spectra that can confound interpretation. ,, Liquid chromatography (LC) with UV detection has previously been employed to differentiate mycobacterial species, and MS/MS has enabled quantitation of alpha-, keto-, and methoxy-MAs in clinical samples and allowed the presence of MAs to be used as diagnostic markers for TB infection. − More recently, MS/MS methods have even been used to identify MAs in archeological material and profile the species as M. tuberculosis .…”

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confidence: 99%

“…37−40 However, the derivatization methods required for GC analysis of cyclopropyl lipid analysis are timeconsuming and are unable to enhance sufficiently the volatilities of all classes of lipids. 37,38,41 Multistage MS methods with collisional activation result in fragmentation at multiple locations adjacent to the cyclopropane ring, yielding convoluted spectra that can confound interpretation. 39,40,42 Liquid chromatography (LC) with UV detection has previously been employed to differentiate mycobacterial species, 43 and MS/MS has enabled quantitation of alpha-, keto-, and methoxy-MAs in clinical samples and allowed the presence of MAs to be used as diagnostic markers for TB infection.…”

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confidence: 99%

Localization of Cyclopropane Modifications in Bacterial Lipids via 213 nm Ultraviolet Photodissociation Mass Spectrometry

2019

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Subtle structural features in bacterial lipids such as unsaturation elements can have vast biological implications. Cyclopropane rings have been correlated with tolerance to a number of adverse conditions in bacterial phospholipids. They have been shown to play a major role in Mycobacterium tuberculosis (M. tuberculosis or Mtb) pathogenesis as they occur in mycolic acids (MAs) in the mycobacterial cell. Traditional collisional activation methods allow elucidation of basic structural features of lipids but fail to reveal the presence and position of cyclopropane rings. Here, we employ 213 nm ultraviolet photodissociation mass spectrometry (UVPD-MS) for structural characterization of cyclopropane rings in bacterial phospholipids and MAs. Upon UVPD, dual cross-ring CC cleavages on both sides of the cyclopropane ring are observed for cyclopropyl lipids, resulting in diagnostic pairs of fragment ions spaced 14 Da apart, thus enabling cyclopropane localization. These diagnostic pairs of ions corresponding to dual cross-ring cleavage are observed in both negative and positive ion modes and afford localization of multiple cyclopropane rings within a single lipid. This method was integrated with liquid chromatography (LC) for LC/UVPD-MS analysis of cyclopropyl glycerophospholipids in Escherichia coli (E. coli) and for analysis of MAs in Mycobacterium bovis (M. bovis) and M. tuberculosis lipid extracts.

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“…A number of studies have exploited mass spectrometrybased lipidomic approaches to define global changes in the lipid composition of mycobacterial and corynebacterial cell envelopes under different growth or drug treatments (14,15,(20)(21)(22). These studies have been greatly facilitated by the development of lipidomics databases, such as Mtb LipidDB (13), MycoMass, and MycoMaps (12) which allow rapid matching of species and facilitate downstream data analysis.…”

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confidence: 99%

Identification of novel lipid modifications and intermembrane dynamics in Corynebacterium glutamicum using high-resolution mass spectrometry [S]

Klatt

Brammananth

O’Callaghan

et al. 2018

Journal of Lipid Research

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The complex cell envelopes of Corynebacterineae contribute to the virulence of pathogenic species (such as and) and capacity of nonpathogenic species (such as ) to grow in diverse niches. The Corynebacterineae cell envelope comprises an asymmetric outer membrane that overlays the arabinogalactan-peptidoglycan complex and the inner cell membrane. Dissection of the lipid composition of the inner and outer membrane fractions is important for understanding the biogenesis of this multilaminate wall structure. Here, we have undertaken the first high-resolution analysis of inner and outer membrane lipids. We identified 28 lipid (sub)classes (>233 molecular species), including new subclasses of acylated/acetylated trehalose mono/dicorynomycolic acids, using high-resolution LC/MS/MS coupled with mass spectral library searches in MS-DIAL. All lipid subclasses exhibited polarized distributions across the inner and outer membrane fractions generated by differential solvent extraction. Strikingly, deletion of the TmaT protein, which is required for transport of trehalose corynomycolates across the inner membrane, led to the accumulation of triacylglycerols in the inner membrane and to suppressed synthesis of phosphatidylglycerol and alanylated lipids. These analyses indicate unanticipated connectivity in the synthesis and/or transport of different lipid classes in .

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Lipid metabolism in mycobacteria—Insights using mass spectrometry-based lipidomics

Cited by 15 publications

References 49 publications

Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy

Metabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy

Localization of Cyclopropane Modifications in Bacterial Lipids via 213 nm Ultraviolet Photodissociation Mass Spectrometry

Identification of novel lipid modifications and intermembrane dynamics in Corynebacterium glutamicum using high-resolution mass spectrometry [S]

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